Cell-Specific α-Tubulin Isotype Regulates Ciliary Microtubule Ultrastructure, Intraflagellar Transport, and Extracellular Vesicle Biology

Curr Biol. 2017 Apr 3;27(7):968-980. doi: 10.1016/j.cub.2017.02.039. Epub 2017 Mar 16.


Cilia are found on most non-dividing cells in the human body and, when faulty, cause a wide range of pathologies called ciliopathies. Ciliary specialization in form and function is observed throughout the animal kingdom, yet mechanisms generating ciliary diversity are poorly understood. The "tubulin code"-a combination of tubulin isotypes and tubulin post-translational modifications-can generate microtubule diversity. Using C. elegans, we show that α-tubulin isotype TBA-6 sculpts 18 A- and B-tubule singlets from nine ciliary A-B doublet microtubules in cephalic male (CEM) neurons. In CEM cilia, tba-6 regulates velocities and cargoes of intraflagellar transport (IFT) kinesin-2 motors kinesin-II and OSM-3/KIF17 without affecting kinesin-3 KLP-6 motility. In addition to their unique ultrastructure and accessory kinesin-3 motor, CEM cilia are specialized to produce extracellular vesicles. tba-6 also influences several aspects of extracellular vesicle biology, including cargo sorting, release, and bioactivity. We conclude that this cell-specific α-tubulin isotype dictates the hallmarks of CEM cilia specialization. These findings provide insight into mechanisms generating ciliary diversity and lay a foundation for further understanding the tubulin code.

Keywords: C. elegans; cilia; extracellular vesicles; glutamylation; intraflagellar transport; kinesin-3; microtubule; polycystin; post-translational modifications; tubulin.

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans / ultrastructure*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Electron Microscope Tomography
  • Male
  • Microscopy, Electron, Transmission
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Tubulin / genetics
  • Tubulin / metabolism*


  • Caenorhabditis elegans Proteins
  • Protein Isoforms
  • Tubulin